To circumvent the severe toxicity of the systemic delivery of IL-12 protein and, tlie limits of local administration of IL-12 gene, we constructed a polymersome system for systemic delivery of recombinant, murine plasmid. (pmIL-12) based on amphiphilic polyphosphaiefieS containing weakly cationic N,N-diisopropylethylenediamine (DPA) as hydrophobic groups and monomethoxy poly(ethylene glycol) (mPEG) as hydrophilic tails. By simple dialysis method, prnIL-12 was successfully loaded into polymersomes clue to the combination-effect-of physical encapsulation and electrostatic interaction. This pmIL-12 polymersome delivery system was validated with good biocompatibility and stability despite of serum protein and DNase challenging. The results;of in-vivo -antitumor experiments showed,that intravenous injection of pmIL-12 polymersomes achieved significant suppression of tumor growth in BALB/c mice bearing CT-26 colon carcinorna. The analysis revealed that 'the mechanism was related to-the antitumor immune response induced by efficient transfection of pmIL-12 polymersomes, which maybe-involved lymphocytes infiltration and angiogenic inhibition at the tumor site.